Carboxamidooxyalkanoic acids



United States Patent O 3,504,008 CARBOXAMIDOOXYALKANOIC ACIDS Ralph P. Neighbors, Olathe, Kans., assignor to Gulf Research & Development Company, Pittsburgh, Pa., a corporation of Delaware No Drawing. Application May 26, 1967, Ser. No. 641,487, now Patent No. 3,449,113, dated June 10, 1969, which is a continuation-in-part of application Ser. No. 374,813, June 12, 1964. Divided and this application Nov. 6, 1968, Ser. No. 798,521

Int. Cl. C07c 101/00 U.S. Cl. 260453 4 Claims ABSTRACT OF THE DISCLOSURE Carboxamidooxyacetic and propionic acids which are useful as selective herbicides are prepared by formation of the amides of aminooxyacetic and aminooxypropionic acids with other monocarboxylic and dicarboxylic acids.

SUMMARY OF INVENTION This application is a division of U.S. Ser. No. 641,487, now U.S. Patent 3,449,113, which was filed on May 26, 1967 as a continuation-in-part of U.S. Ser. No. 374,813 filed June 12, 1964 now U.S. Patent 3,457,063 in which it was disclosed that various aminooxy compositions are useful as selective herbicides. The prior application disclosed a variety of types of selectivity among the different compounds, there being no obvious correlation between variations in structural formula and the activity or selectivity in most instances. In U.S. Ser. No. 543,879, now U.S. Patent 3,396,009, which was also a continuationin-part of U.S. Ser. No. 374,813 there isdisclosed a method of combating weeds in sugar beets, using benzamidooxyacetic acid in either acid or water-soluble salt form. The present application is directed to use of one class of compositions, the carboxamidooxyalkanoic acids and their water-soluble salts.

The novel compounds of this invention are useful in the method of combating undesired plant growth which comprises applying to the locus of the plant a.herbicidally effective amount of a compound selected from carboxamidooxyalkanoic acids and their water-soluble salts represented by the general structural formula in which X represents a member of the group consisting of 3,504,008 Patented Mar. 31, 1970 ice R represents a member of the group consisting of hydrogen, methyl and lower alkyl, n may vary within the range of zero to two and Y is selected from hydrogen and cations,

DETAILED DESCRIPTION OF THE INVENTION So as to make clear the characteristics of the selective herbicides employed in the method, the procedure and results of controlled comparative tests on a variety of plant species are presented below.

EXPERIMENTAL PROCEDURE FOR HERBICIDE USE A water suspension of the chemical is prepared by combining 0.4 gram of the chemical to be tested With 4 ml. of a solvent mixture (3 parts Emulphor EL-7l9 combined with one part xylene and one part kerosene) and then adding sufiicient Warm Water to make 40 ml. of mixture. Emulphor EL-719 is described as a polyoxyethylated vegetable oil.

Oats, wheat, peas, radish, flax, millet, alfalfa, tomatoes, and sugar beets are planted in 4 in. pots in the greenhouse. Ten to eighteen days after the emergence of the plants, they are sprayed with the above prepared water emulsions at a rate of 5 pounds of the active chemical per acre and a spray volume of 60 gallons per acre. Seven days after application, the plants are observed and the results of the treatment are as shown in the table.

The plants are rated as follows:

C=Chlorosis (bleaching).

N=Necrosis.

G=Growth inhibition.

K=Non-emergence.

F=Formative eifect (abnormal form of growth).

0=No effect.

1=Slight eifect.

2=Moderate eifect.

3=Severe efIect.

4=Maximum elfect or dead plants.

TABLE Post-emergent activity at 51b./acre Structural Formula of Compound Tomato Millet Flax b e il s Corn Wheat Oats Radish iti' t s Alfalfa O H CH @d-N-o-(JE-C 0 OH N4 N4 N1 N4 G3, N1 N2 N1 N2 N4 N1, G2

(M.P. 132-3 0.) i

O H i )l IOCH-O O OH N4 N4 G2, N1 N4 N4 N4 N2 N4 N4 N4 01 O H CH3 Cl(ilN-O-CHCOOH N4 N2 N1, G2 G2 F1, G2 N1 N1 N2 I N4 N1 Post-emergent activity at 5 lb./aere Structural Formula of Compound Tomato Millet Flax b s Corn Wheat Oats Radish i e efi Alfalfa O H OI( JNOCHzCOOH N4 N4 N2 G2, 01 N1 N2 C1 02 N4 N2 Cl 0 H Cl--NO CHz-COOH N4 N4 N3 G2 N1 N2 N1 N4 N4 N2 0 H Cl-QQJ-N-OCHz-OOOH N4 N4 G2, N2 G1 N1 N1 0 0 N2 0 (in (M.P. 168-70) 0 H CH3 J JN-O-JJHOOOH N4 N3 N1 F2, G2 N1 N1 0 N1 N1 F1, N1

0 H -(JIlT-OOflz-O 0 0K N4 N4 N2 G3, N3 G3, N3 N1 N1 N3 N4 0 (Deeomp. 193") Post-emergent activity at 51b./acre Soy- Sugar Structural Formula of Compound Tomato Millet Flax beans Corn Wheat Oats Radish Beets Alfalfa i 1 CH3NO-CII2CH2C O 011 N4 N4 N4 N3, G4 N4 N3 N3 N4 N4 G2, G2

(M.P. 8890 C.)

CHr-C O OH IIzC :(|3I|IO CH2-C O ONa N4 F1 N1, G3 N1, G2 0 0 N2 G2 0 H C-0 0 OH H (lf-NOOHz-COONa N4 N4 G2 G2 G3 N4 N4 N4 0 C O OH fi-NOCHzCOOa N4 N4 N4 G1 N4 G2 N4 N4 N4 (M.P. over 250) HzC-C O OH Hz C|lN-OCHz-O O ONa N4 G3 G3 G3 N4 G3 N4 N4 G3 H2OC O OH Hz( J-CHT-CITI IIOCH2-O O ONa N4 N4 G3 G2 N1 G1 G2 N4 N4 G2 Upon reduction of the rate of application, selective characteristics of the herbicides become more pronounced. Furthermore, some of the specifically exemplified compounds are also effective as pre-emergent herbicides. This is true of the compound having the structural formula:

OOOH

and its water-soluble salts. This compound is particularly useful in combating weeds in corn. Benzamidooxyacetic acid and its water-soluble salts have been found to possess unusual utility for combating certain weeds in sugar beet fields. The method of accomplishing this specific purpose is the subject of U 5. Ser. No. 543,789 filed Apr. 20, 1966 as a continuation-in-part of U.S. Ser. No. 374,813.

MANUFACTURE OF HERBICIDES PREPARATION OF 3-AMINOOXYPROPIONIC ACID HYDROCHLORIDE A mixture of methyl 3-isopropylideneaminooxypropionate (15.0 g., 0.094 mol derived from acetone oxime and methyl acrylate) concentrated hydrochloric acid (75 ml.), and water (75 ml.) was stirred and heated to boiling. Approximately ml. of distillate was collected, then the residual mixture was stripped under reduced pressure and the residue stirred 1 hour with isopropyl alcohol (100 ml.) Filtration and subsequent crystallization from an ethanolether mixture gave 7.3 g. (55%, M.P. 152-4 C.) of the desired compound.

Analysis. Calculated for C H CINO (percent): C, 25.46; H, 5.68; N, 9.90. Found (percent): C, 25.76;.H, 5.49; N, 9.99.

PREPARATION OF 3-ACETAMIDOOXYPROPIONIC ACID S-aminooxypropionic acid hydrochloride (14.1 g., 0.1 mol), acetic anhydride (15.3 g., 0.15 mol), and glacial acetic acid was stirred, heated, and refluxed 4 hours. The

PREPARATION OF m-CHLOROBENZAMIDOOXY- ACETIC ACID A mixture of m-chlorobenzohydroxamic acid (0.1 mol, 16.5 g.), bromoacetic acid (0.1 mol, 13.9 g.), sodium hydroxide (0.2 mol, 8.0 g.), ethanol ml.), and water (150 ml.) was stirred, heated, and refluxed 5 hours. The mixture was then cooled and acidified with dilute hydrochloric acid. The mixture was then extracted with ethyl acetate (2x 250 ml.) and the extracts were combined and dried over magnesium sulfate. Dilution of the dried extract with n-hexane precipitated the desired product which was removed by filtration and dried. There was obtained 17.1 g. (74%, M.P. 153-5 0.).

Calculated for C H ClNO (percent): C, 47.07; H, 3.51; N, 6.10; Cl, 15.44. Found (percent): C, 47.25; H, 3.86; N, 5.74; Cl, 15.44.

PREPARATION OF N-(ETHOXYCARBONYL) AMINOOXYACETIC ACID Bromoacetic acid (0.2 mol) was dissolved in water (50 ml.) and neutralized to a phenophthalein end-point with 10% sodium hydroxide. N-hydroxyurethane (0.2 mol) was added, followed by the addition of sodium hydroxide (0.2 mol). The mixture was stirred 2 hours at room temperature, then concentrated to ml. volume under reduced pressure. The concentrate Was acidified with dilute HCl and extracted with ethyl acetate (3X ml.). The extract was dried over magnesium sulfate and the solvent removed under reduced pressure. The residue was stirred with benzene (250 ml.) until crystalline, filtered, washed with hexane and dried. There was obtained 16.0 g. of product (M.P. 779 C.).

Analysis. Calculated for C H NO (percent): C, 36.81; H, 5.56; N, 8.58. Found (percent): C, 36.49; H, 5.48; N, 8.13.

PREPARATION OF N-(METHOXYCARBONYL) AMINOOXYACETIC ACID Aminooxyacetic acid hemi-hydrochloride (11.99 g., 0.11 eq.), acetic acid (50 ml.) and methyl chloroformate (9.4 g., 0.1 mol) were stirred, heated and refiuxed3 hours. The mixture was cooled and volatile material removed under reduced pressure. The residue was extracted with hot ethyl acetate ml.) and the extract diluted with hexane (400 ml.) and stirred overnight. The product was removed by filtration and dried giving 8.7 g. (M.P. -87 C.).

Analysis. Calculated for C H NO (percent): C, 32.22; H, 4.73; N, 9.39. Found (percent): C, 32.35; H, 4.82; N, 9.21.

PREPARATION OF SODIUM N-(3-CARB OXY- PROPIONYL) AMINOOXYACETATE Aminooxyacetic acid hemi-hydrochloride (10.9 g., 0.1 eq.) and methanol ml.) were stirred while immersed in an ice bath. This solution was neutralized to a phenophthalein end-point by the dropwise addition of a solution of sodium methoxide in methanol. The neutralized mixture was stirred 30 min., then filtered to remove sodium chloride. The filtrate was added to a solution of succinic anhydride (0.1 mol) in methanol (300' ml.). This mixture was stirred 30 minutes and the product removed by filtration, washed with methanol (100 ml.) and dried. There was obtained 16.1 g. (M.P. 178-80 C.) of the desired product.

Analysis.Calculated for C H NaNO (percent): C, 33.81; H, 3.78; N, 6.57; Na, 10.79. Found (percent): 33.75; H, 3.99; N, 6.20; Na, 10.66.

In controlling plant growth by means of herbicides it is necessary to obtain penetration of the formulation through waxy protective layers to obtain contact with plant fluids, and once contact is obtained, water solubility is desirable so as to cause the systemic migration of the herbicide. Water solubility and ability to penetrate or dissolve waxy cuticle are characteristics which seldom appear in a single substance and, in most instances, 55

surface active agents in herbicide formulations. Further more, when using highly active herbicides, it is difficult to obtain uniform distribution of a small quantity of material unless it is dispersedor dissolved in a larger quantity of diluent before application. Preferred diluents are water and inert solids. From a practical standpoint, water is the preferred diluent because it is cheap and sprayapplication is more convenient than dusting. The preferred formulations for use in the present method are water-dispersible solutions of herbicides in organic solvents or dispersible powders. The herbicides themselves are soluble in water in the form of water-soluble salts, so they may be sold and transported as concentrated aqueous solutions. In warm climates where there is no danger of freezing and breaking containers, aqueous solutions may be preferred, especially solutions of sodium or ammonium salts.

What is claimed is:

1. The compound corresponding to the formula om-r'i-fz-o-om-on-o 0 on 2. The compound corresponding to the formula H C-NOCH2COOH 3. The compound corresponding to the formula 1120-00011 H2(|)CN-O OHzC 0 OH III 4. The compound corresponding to the formula OOOH References Cited UNITED STATES PATENTS 3,187,041 6/ 1965 Richter.

3,187,042 6/ 1965 Richter.

3,282,987 ll/ 1966 Ellis.

3,420,824 1/ 1969 Ellis 260-453 X OTHER REFERENCES Schumann et al., Journal of Medicinal and Pharmaceutical Chemistry, vol. 5, pp. 464-476 (1962).

CHARLES B. PARKER, Primary Examiner S. T. LAWRENCE III, Assistant Examiner US. Cl. X.R.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Ralph P. Neighbors Inventofls) It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

In the heading to the printed specification, lines 3 to 5, "Gulf Research 6 Development Company, Pittsburgh, Pa., a corporation of Delaware" should read Gulf Oil Corporation,

Pittsburgh, Pa., a corporation of Pennsylvania Signed and sealed this 2nd day of November 1971.

(SEAL) Attest:

EDWARD M.FLETCHER,JR. ROBERT GOTTSCHALK Attesting Officer Acting Commissioner of Patents FORM PO-1050 (10-69) 

